Study of the regulation of alternative polyadenylation of precursors of messenger RNA by the energetic metabolism and aging in Saccharomyces cerevisiae

• Grant number: 14/26774-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2015
• End date: February 29, 2016
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Mario Henrique de Barros
• Grantee: Erich Birelli Tahara
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

In eukaryotes, RNA polymerase II is responsible for the transcription of the precursors of messenger RNA, which undergo an extensive co-transcriptional processing whose final result is their maturation. Except for the transcripts of histone genes, the precursors of every other messenger RNAs present endonucleolytic cleavage and polyadenylation at their 3' ends. Notably, the cleavage/ polyadenylation can occur at more than one site of a given RNA precursor, characterizing a phenomenon known by alternative polyadenylation. Interestingly, alternative polyadenylation is also able to give rise to messenger RNAs devoid of stop codons, since cleavage/polyadenylation sites can be found within the coding sequence of some RNA precursors. Although it has been known that the alternative polyadenylation is modulated by the energetic metabolism, and also by stress conditions, the molecular mechanisms whereby the cleavage/polyadenylation machinery is specifically directed to one between all the available sites for its activity in certain metabolic conditions remain poorly understood. Moreover, the impact of the formation of a messenger RNA lacking its stop-codon by alternative polyadenylation also have yet to be determined in the context of protein synthesis quality control and lifespan of S. cerevisiae. Therefore, this proposal intends to contribute to the knowledge (i) of how alternative polyadenylation is regulated during the metabolic history of S. cerevisiae; (ii) of how this phenomenon correlates with the metabolism of defective proteins synthesized from messenger RNAs devoid of stop codons; and (iii) to which extent alternative polyadenylation defects influences the lifespan of this organism. (AU)